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首页> 外文期刊>Japanese Journal of Cancer Research >Sequential histopathological changes in vivo after suicide gene therapy of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.
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Sequential histopathological changes in vivo after suicide gene therapy of gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

机译：N-甲基-N'-硝基-N-亚硝基胍诱导的大鼠胃癌自杀基因治疗后体内的顺序组织病理学变化。

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摘要

Gastrointestinal cancer is the most important clinical target of gene therapy. Suicide gene therapy, such as with the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene, has been shown to exert antitumor efficacy in various cancer models in vitro. We previously reported in situ gene transfer and gene therapy for gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in dogs. Here, we describe the sequential histopathological changes after suicide gene therapy of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer in rats. Gastric tumors were induced by MNNG in 38 / 73 (52%) of Wistar strain rats. The suicide gene therapy group (14 rats) was subjected to in situ gene transfer with a recombinant adenovirus vector carrying the HSV-TK gene driven by CAG promoter (Ad.CAGHSV-TK) in gastric tumor, followed by the antiviral drug ganciclovir (GCV). To observe the histopathological changes at various times after HSV-TK / GCV gene therapy, groups of animals were sacrificed at 3, 8, and 30 days after gene transfer. Apoptosis in the gastric tumors was detected by the TUNEL method to assess the efficacy of HSV-TK / GCV gene therapy, and it was marked in the 8- and 30-day treatment groups compared to the sham operation controls (P < 0.001). Various histopathological changes, degeneration of cancer tissue and fibrosis after necrosis and apoptosis were significantly greater in the 30-day treatment group. The HSV-TK gene was detectable in peripheral blood by PCR until 30 days after gene transfer. These results may be useful in devising a method of suicide gene therapy for humans.
机译：胃肠道癌是基因治疗最重要的临床目标。自杀基因疗法，例如使用单纯疱疹病毒1型胸苷激酶（HSV-TK）基因，已在多种体外癌症模型中发挥抗肿瘤功效。我们以前报道了由N-乙基-N'-硝基-N-亚硝基胍（ENNG）诱导的犬胃癌的原位基因转移和基因治疗。在这里，我们描述了自杀基因治疗N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的大鼠胃癌后的组织病理学变化。 MNNG在38/73（52％）的Wistar品系大鼠中诱发了胃肿瘤。自杀基因治疗组（14只大鼠）用重组腺病毒载体进行原位基因转移，该载体带有胃癌中由CAG启动子（Ad.CAGHSV-TK）驱动的HSV-TK基因，然后是抗病毒药更昔洛韦（GCV） ）。为了观察HSV-TK / GCV基因治疗后不同时间的组织病理学变化，在基因转移后第3、8和30天处死动物。通过TUNEL方法检测胃肿瘤中的细胞凋亡，以评估HSV-TK / GCV基因疗法的疗效，与假手术对照组相比，在第8天和第30天的治疗组中有明显的细胞凋亡（P <0.001）。在30天的治疗组中，各种组织病理学变化，癌组织的变性以及坏死和凋亡后的纤维化明显增加。直到基因转移后30天，才可以通过PCR在外周血中检测到HSV-TK基因。这些结果可能有助于设计一种针对人类的自杀基因疗法。

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